Deficiency of IL-22 Contributes to a Chronic Inflammatory Disease: Pathogenetic Mechanisms in Acne Inversa
| Autor: | Robert Sabat, Ansgar Lukowsky, Katrin Witte, Ellen Witte, Annette Buss, Hans Joachim Roewert, Wolfram Sterry, Stefanie Kunz, Kerstin Wolk, Katarzyna Warszawska, Sylke Schneider-Burrus, Markus Krause, Hans-Dieter Volk, Conny Hoeflich |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Male Adolescent medicine.medical_treatment T cell Immunology Population Biology Interleukin 22 Pathogenesis Mice Young Adult Downregulation and upregulation medicine Animals Humans Immunology and Allergy Hidradenitis suppurativa Receptor education Cells Cultured Aged Inflammation Mice Inbred BALB C education.field_of_study Interleukins Middle Aged medicine.disease Hidradenitis Suppurativa Up-Regulation Cytokine medicine.anatomical_structure Chronic Disease Cytokines Female Inflammation Mediators Antimicrobial Cationic Peptides |
| Zdroj: | The Journal of Immunology. 186:1228-1239 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Overexpression of the T cell cytokine IL-22 is linked to the development of some chronic diseases, but little is known about IL-22 deficiency in humans. As demonstrated in this study, acne inversa (AI; also designated as Hidradenitis suppurativa) lesions show a relative deficiency of IL-22 and IL-20, but not of IL-17A, IL-26, IFN-γ, IL-24, or IL-1β. Moreover, AI lesions had reduced expression of membranous IL-22 and IL-20 receptors and increased expression of the natural IL-22 inhibitor, IL-22 binding protein. AI is a chronic inflammatory skin disease with prevalence up to 4% of the population and in which cutaneous bacterial persistence represents an important pathogenetic factor. Accordingly, we also found a relative deficiency of antimicrobial proteins (AMPs) in AI lesions and a positive correlation between lesional IL-22 and IL-20 versus AMP levels. IL-22, like its tissue cell downstream mediator IL-20, upregulated AMPs in reconstituted human epidermis and was critical for increased AMP levels under inflammatory conditions. The relative IL-22 deficiency in AI was not linked to lesional T cell numbers or Th22/Th1/Th17 subset markers and -inducing cytokines. However, IL-10 was highly expressed in AI lesions and correlated negatively with IL-22 expression. Moreover, IL-10 inhibited IL-22 but not IL-17 production in vitro. The IL-10 overexpression, in turn, was not associated with an elevated presence of regulatory T cells but with the enhanced presence of an IL-10–inducing cytokine. We conclude that IL-22 deficiency may contribute to the pathogenesis of certain chronic disorders as postulated in this paper for AI. |
| Databáze: | OpenAIRE |
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